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PREFACE
The study of health in the history of Jefferson County, Alabama illuminates the structure and values of our society as well as the nature of medicine and the health sciences. The collection of the documents of this exciting history is the mission of the JCMS/UAB Health Sciences Archives; and this paper, the first in a series of Occasional Papers, is a logical product of the collecting and curating activity.
In addition to collection development, the Archives engages in public outreach activities such as traveling historical displays, an audio-visual production and oral history projects. Oral history preserves the recollections of people who have participated in and witnessed the making of history – in this case the histories of our hospitals, medical schools, private practices and public institutions. Subsequent issues in the Occasional Paper series will present stimulating extracts from the oral history projects.
The author of this paper, Linda Casselman Akenhead, is a product of the graduate history program of the University of Alabama at Birmingham, and her research on Dr. Tom Douglas Spies originated under the direction of Professor Virginia Van der Veer Hamilton. Ms. Akenhead's interest in the history of medicine and nutrition in particular is grounded in her past experience as a clinical dietician. She also served as a member of the JCMS Archives Committee and researched the history of medicine in Jefferson County for the Archives' audiovisual production.
The JCMS/UAB Health Sciences Archives thanks Dean James A. Pitman, Jr., M.D., for his support of the Archives, especially the Occasional Papers project.
Virginia Fisher
Archivist
In the American South of the early twentieth century, pellagra symbolized poverty. Frequently referred to as the "scourge" or "lazy" disease by the Northern press, pellagra afflicted sharecroppers and tenant farmers as well as mill and mine workers. Low income farmers and working people could not afford expensive perishable food; therefore, these men, women, and children existed on relatively cheap food items available through a company commissary or rural grocery store such as cornmeal, molasses, salt pork, and dried beans.
Depression gripped the South in the 1920's, resulting in a Public Health Service prediction that collapse of the cotton market would result in an increase of pellagra cases. A storm of objections from Southern politicians, businessmen, and physicians met this announcement; because pellagra was a symbol of poverty, these leaders denied that the South was a victim of widespread "hidden hunger." Yet pellagra afflicted thousands of people in the area; not until 1945 were most vestiges of the disease eradicated from the South. In part, the eradication of pellagra was due to the disappearance of company owned mill towns and the disappearance of cotton tenantry. However, a major breakthrough in the conquest of pellagra is attributed to the successful experimentation of Dr. Tom Spies during the late 1930’s with the use of nicotinic acid in treating pellagra at the nutrition clinic in Hillman Hospital-- now a part of the Medical Center of the University of Alabama at Birmingham. Interestingly, pellagra was first identified as endemic in Alabama in 1906; it was also in this state that the work of Dr. Tom Douglas Spies contributed to the successful eradication of the disease.
Spies (rhymes with "fees") was born September 21, 1902 in Ravenna, Texas. He received his B.A. from the University of Texas in 1923 and his M.D. from Harvard Medical School in 1927. He came to Alabama in 1936 at the invitation of Dr. J. S. McLester, Physician-in-Chief of Hillman Hospital, and remained in Birmingham almost a quarter of a century. Spies held five teaching positions, was affiliated with many medical organizations, wrote a number of major articles and texts, and received plaudits from a number of organizations both local and international.
Spies first became aware of pellagra as a child when he joined his two physician uncles on rounds to the homes of ranchers and farmers in an area called Red River Valley in Texas. He was troubled by his uncles' inability to cure the disease. Later in 1930, as an intern at Lakeside Hospital in Cleveland, Ohio, he treated his first pellagra patient. Although Spies administered the Goldberger diet - the recommended therapy of that time- the patient died. He blamed this failure on the fact that his patient did not eat enough food. After reviewing the hospital records of patients with pellagra, he discovered that 54% of all patients afflicted with the disease died. Spies set out to find the cure for pellagra. This determination provided the treatment that would finally eradicate pellagra.
Unmarried - although he claimed to be married to his work - and having few interests outside of medicine, Spies concentrated on his medical research. Friends adored him and used such terms as "gentle" and "magnanimous" to describe Spies's personality. He considered his employees as “family” and frequently entertained them with dinners at the local country club. It was not unusual for them to receive a thank-you note or birthday card from Spies. He had a knack for remembering names and dates. He was not a church-goer, claiming that he could accomplish more for the human race by spending his time in his clinic rather than in church. One of Spies's former associates, Dr. Hady Lopez, described Spies as "an independent man who made his decisions acting on his own and with the intellectual capacity to direct others in carrying out his wishes.”
Spies devoted his life to advancing the science of nutrition. He is credited with a number or discoveries at this nutrition clinic in Birmingham: among these are the use of synthetic folic acid for pernicious anemia; the use or riboflavin for diseases of the eye; and the use of thiamin for beriberi and heart disease. But he is most noted for his successful Alabama experiments with nicotinic acid in the treatment and prevention of pellagra. In order to understand the importance of Spies' work with pellagra, a brief summary of the disease is helpful.
Pellagra is caused by a deficiency of niacin which is one of the B-complex vitamins. Niacin is synthesized in the human from the amino acid tryptophan and therefore is an anti-pellagra factor. Foods such as milk and meat are good sources of tryptophan which occurs in crude protein. Corn, however, in addition to being deficient in niacin, is also deficient in tryptophan. People whose diet centers around corn are therefore pellagra prone. Characteristics of the disease include symptoms of dermatitis, anorexia, weakness, diarrhea. The tongue becomes thickly coated and the mouth extremely sore. Mental changes such as confusion, loss of memory, depression, and delirium may occur in more advanced cases. Pellagra did not respect age, sex, or race. A marked feature of the disease was the seasonal prevalence in the spring following the restricted and inadequate diet through the winter months.
To explain this mysterious disease, early medical researchers advanced a number of theories. The most widely accepted theory attributed pellagra to corn since this was the major dietary staple in districts with endemic pellagra in Italy during the nineteenth century. In 1872, Cesare Lombroso, an Italian physician, attributed pellagra to a toxin or bacteria on spoiled corn; this theory remained popular for many years. In 1911, the Illinois Pellagra Commission concluded that the primary etiological factor was a living micro-organism of unknown nature, the probable source of infection being through the intestinal tract. Early treatments for pellagra included transfusions of blood from recovered pellagrins; large doses of castor oil; static electricity; or - for those who could afford it – a trip to the healing waters of mineral springs.
In 1906, the first signs of endemic pellagra in the United States were discovered by Alabama's Dr. George Searcy who recognized pellagra in patients at the Hospital for the Colored Insane at Mount Vernon, Alabama. It was the same disease that had occurred or reappeared in a few patients at Mount Vernon every year since 1901. In his 1908 address to the Medical Association of the State of Alabama, Dr. Searcy noted that during the summer of 1906, there were eighty-eight cases of pellagra, with a mortality rate of sixty-four percent at the Mount Vernon Hospital. The average age of the patients was thirty- four years; two-thirds of these had been in the hospital longer than one year. In trying to determine the cause of pellagra, Dr. Searcy noticed that not one of the hospital staff members had any symptoms of the disease. Comparing the diets of staff members and patients, he observed that patients received damaged corn with their meals. He sent a sample of the corn to Washington, D.C. where it was pronounced unfit for human consumption. Dr. Searcy removed the damaged corn and grits from the patients' diets, substituting wheat bread and potatoes. Within ten days no new cases appeared.
Armed with this knowledge, Dr. Searcy warned other physicians to be alert for signs for pellagra because much of the 1905 Western corn crop had been damaged by wet weather. Following Dr. Searcy's warning, Southern doctors reported nine cases of pellagra at the State Hospital for the Insane at Columbia, South Carolina, and forty cases of pellagra resulting in twenty-three deaths at the Georgia State Sanitarium in Milledgeville.
Although Dr. Searcy's discovery helped physicians become aware that pellagra existed in the United States, it still did not solve the problem of how to treat it. Pellagra was now appearing in more Southern states than in any other section or the country. According to the 1912 Surgeon General's Report on the geographical distribution of pellagra in the United States, the lower Southern states were at a higher risk for pellagra outbreaks. In Alabama alone, the two counties with the highest incidence of pellagra were Jefferson, reporting 225 cases of pellagra, and Clark, reporting 155 cases. Dr. Lewis Coleman Morris of Birmingham, in an annual address to the Southern Medical Association in 1912, noted that “despite all or our efforts up to this time the prevent ion of this disease remains obscure.”
By 1913 the total number of deaths from pellagra in Alabama alone exceeded 500 cases, and the disease now ranked behind tuberculosis, pneumonia, and typhoid fever as causing the greatest number or deaths from infectious disease in the state. Fear that the disease was communicable led to drastic measures of isolation and quarantine. The Alabama State Board of Health, for example, issued a recommendation that pellagrins be "thoroughly isolated in reference to clothing, bedding, and the use of crockery."
Several factors contributed to the rise of pellagra in the South. The crop-lien system imposed a vicious cycle on Southern agriculture. To repay loans, many farmers had to plant their land with the most marketable cash crop - cotton. The lower the price of cotton, the more a farmer had to plant in order to meet his debts. This reduced the amount of land devoted to food crops and animals. Farmers who might otherwise have produced their own food became more dependent on merchants for their supplies. Since they were forced to rely on market prices, cotton futures, and credits, sharecroppers and tenant farmers were unable to afford expensive perishable foods.
In addition, the change in the character of the corn meal contributed to the rise in pellagra. Before 1900, most meal used in smaller towns and practically all consumed in rural areas was ground by small local grist mills. At the turn of the century finely bolted meal produced by large milling companies appeared. This so-called Western meal was thoroughly degerminated to prevent rancidity during storage and shipment. This resulted in all essentially vitamin-free product. Within a few years, the corn meal and other staple cereal foods of millions of people changed from what was essentially a vitamin-rich whole grain product to a highly refined carbohydrate that contained practically no essential vitamins or other nutrients.
Finally in 1915, an early breakthrough in the etiology of the disease was announced at the National Pellagra Conference in Columbia, South Carolina. According to Dr. Joseph Goldberger, "an unbalanced diet has been fully and scientifically demonstrated to be the cause of pellagra and the disease has been cured by changing the diet to include peas, beans, and milk.” Goldberger began his study of pellagra in 1914 when the Public Health Service placed him in charge of identifying its causes. Goldberger made repeated trips throughout the South visiting mental hospitals and orphan asylums in Georgia, Alabama, Florida, Kentucky, and Mississippi where pellagra was most prevalent. Goldberger checked the diet of each patient and found that they lacked sufficient amounts of eggs, milk, and meat. He noticed that the high carbohydrate content of the diets came from cornmeal, white flour, sugar molasses, fat pork, and polished rice. In order to test the theory that pellagra was caused by a faulty diet, and not by an infection as many medical doctors assumed, Goldberger and his wife ingested or injected samples of effluvia from very ill victims of pellagra. Having found no infection, he returned to his study of diet. This time he induced pellagra on healthy white male convicts at the Rankin farm of the Mississippi State Penitentiary by feeding the same monotonous, principally cereal diet, which he had found in orphanages and mental hospitals. This experiment reinforced his belief that pellagra resulted from a dietary deficiency in certain classes or food. But a large portion of Southern medical professionals were reluctant to accept the Goldberger "diet theory" as the only etiological factor in pellagra. The idea that a disease was brought on by something "you did not eat" was unheard of at this time.
Undaunted, Goldberger continued his studies – this time in seven South Carolina mill villages. From April 1916 to December 1916, Goldberger carried on a bi-weekly house-to-house search for cases of pellagra. Comparing the diets of families with pellagra and those without the disease revealed that the latter consumed a more liberal supply of animal protein foods (lean meat, milk, cheese. and eggs). Goldberger then drew a correlation between diet and economics. In general, as income fell, the incidence of the disease rose and showed an increasing tendency to affect members of the same family. Goldberger again reiterated that a faulty or unbalanced diet resulted in pellagra.
Goldberger had not publicly announced his mill village findings until the summer of 1921 when economic prosperity began to decline. He sent a letter to the Public Health Service headquarters in Washington stating: "For all practical purposes we have in our own country this summer thousands of people who are starving and dying ... We are feeding the Near East and the Far East but we are neglecting our own people here at home.” The Public Health Service joined Goldberger in announcing that an epidemic of pellagra among farmers forced into starvation diets would occur due to the collapse of the cotton market and the "ravages" of the boll weevil. A storm of objections and abuse met this announcement. Local public health officials denied that there was "hidden hunger" in the South. Birmingham physician, Dr. Seale Harris, wrote an editorial to the Southern Medical Association criticizing the unfavorable publicity the South had received because of pellagra. Harris declared, in part: "Zealots of food deficiency as the sole cause of pellagra… had missed their mark and left the impression that the South is backward and poverty stricken. They have exaggerated the seriousness of pellagra as a disease.” He further elaborated that this has interfered with the "agricultural development of the most fertile lands in the United States, and it has prevented many industries from locating in the favored South.”
Southern political leaders also denied that pellagra was increasing as did many health departments in Tennessee, Louisiana, Alabama, North Carolina, Virginia, and Georgia. But most state health officers did not know the extent of the pellagra situation in their state since pellagra was not always a reportable disease. Also many business and political leaders denied the existence of a pellagra problem. They rejected Goldberger's efforts to tie pellagra to the basic poverty of the South because they were unwilling to admit that the South was poor. Finally, many Southern physicians rejected Goldberger's findings because they felt nutrition was an area of science suitable for study by chemists, not physicians. Because they were schooled in the bacteriological concept of disease, many doctors found it difficult to accept Goldberger's findings. But Goldberger continued his study of pellagra until 1929 when cancer cut short his career.
Pellagra continued to leave its mark on the South into the 1930's. Between 1920-1935, 58 out of 183 pellagra patients admitted to Birmingham's Hillman
Hospital died from pellagra. Although these patients had received the Goldberger diet, the death rate had not diminished. Despite the interest in pellagra since the early 1900's, physicians were unable to affect the ultimate outcome of severe cases. There was a consistent death rate of one in two to four hospitalized cases.
Dr. James L. McLester, physician-in-chief at Hillman Hospital, had read a 1934 study by Spies describing how he had reduced the mortality rate from 54% to 6% in a series of 125 cases of severely diseased pellagra patients at Lakeside Hospital in Cleveland, Ohio. These cases consisted largely of derelicts, chiefly alcoholics with pellagra, and patients with the disease secondary to other organic conditions. Spies was experimenting with these patients to see if alcohol was a primary factor in the cause of pellagra. He took the derelicts and fed them the Goldberger diet; however, at the same time he allowed them to consume as much corn liquor as they could drink. The pellagra cleared up, indicating that it had not been caused solely by alcohol but by the absence of essential food factors. When he reported the results of his study on the alcoholics to medical conventions and journals, some physicians questioned whether or not his findings would apply to the nutritional status of the people living in the South who were not alcoholics. Spies maintained that pellagra in the South would respond to a similar therapy. Still skeptical, McLester invited Spies to come to Birmingham to prove whether he could keep “doomed pellagrins out of the grave in the South.”
Spies accepted the challenge and selected three people to come with him to Birmingham: a dietician, Jean Grant; a nurse, Ann Van Blaricom; and a medical assistant, Dr. Austin Chinn. Since conditions in the Hillman were very crowded when Spies arrived, he was offered the only space available for carrying out his studies - a hallway which would later become the Hillman Emergency Clinic. During the spring and summer of 1936, Spies tested his feeding regime on fifty critically ill pellagra patients. The treatment consisted of complete bed rest plus very high caloric, high protein diets, with much larger quantities of brewer's yeast and liver than had been used before. When possible, patients consumed approximately 4,000 to 5,000 calories daily with 125 to 130 grams of protein. Each patient received individual attention and dose observation during the experiment. Patients were required to eat all their meals. Substitutions in form and consistency of foods were made when patients had difficulty consuming a regular diet. It often took an hour to force a meal down and see that it stayed down. Sometimes Spies, Grant, or Chinn took twelve hour shifts with the patients seeing that all food was consumed. Brewer's yeast was used as the specific therapeutic agent in those patients who were not vomiting. It was usually given in one-ounce doses mixed in eggnog three or more times daily. When vomiting or diarrhea was present, liver extract – a relatively new method in treating pellagra – was given intravenously in the severest cases, intramuscular in others, every two to three hours to those too sick to eat. Only three patients out of fifty failed to respond to this treatment.
Spies's successful study indicated that pellagra was due to deficiencies in the diet and that there was no difference in response of patients with pellagra in the North or South. But news of his achievements did not impress some medical doctors in the South. They still insisted that endemic pellagra was not the same as the mild Northern variety "caused by alcohol." Yet Spies remained adamant: the irritability, dizziness, and tired feeling of which many pellagra patients complained was due to the "hunger sickness" that gave the South its reputation of being "lazy."
Although Spies came to Birmingham in the early 1930's with the idea of staying only long enough to complete one brief study on pellagra, he found the wealth of clinical material at the Hillman Hospital and Birmingham area conducive to further studies. The staff of Hillman Hospital invited Spies to remain in Birmingham. Following his acceptance, the Department of Internal Medicine of
the University of Cincinnati opened a nutrition clinic at Hillman Hospital in 1937, and granted Spies a yearly nine month's leave-of-absence to work in
Birmingham. Spies declared that “other hospitals would have been available for studies but that Hillman was chosen because of the fine spirit of cooperation and the high standards of the staff.”
When the clinic opened, Spies soon realized that pellagra was not confined within the city limits. Mining villages, camps, and tenant farmers were located outside the city limits. Large numbers of these people had been out of work during the Depression. Many were ill and did not have the strength, energy, nor money to seek assistance. Thus Spies chose to attack pellagra aggressively. Rather than wait for pellagrins to come to Hillman, he and his staff would drive the country roads to Jefferson and neighboring counties looking for victims of the disease. They would seek out the tenant, sharecropper, or mill family. Since the early stages of pellagra were sometimes difficult to identify, Spies' "clinical test" to determine pellagra was to look at the family dog. Pets, eating scraps from the tables of persons who ate a pellagra-producing diet, tended to develop black tongue (a disease analogous to pellagra in humans). This observation provided Spies with a reliable indicator that family members would be afflicted with pellagra.
Because of his warm and friendly attitude towards these people, Spies gained acceptance into their homes. When symptoms of pellagra were found in a family, Spies often brought them back to Hillman for treatment. Those with advanced cases remained in the hospital. Detailed diet and social histories were obtained. Diet histories of all families generally revealed a high carbohydrate and low protein diet consisting of fatback, always cornbread, a few greens for those who could afford a small garden, molasses, and alcohol for those who had a still. As patients began to improve, staff members counseled them on how to diversify their diets. Word got around about the nutrition clinic and patients began to seek treatment.
Free transportation provided the incentive to get patients to come to the clinic for treatment. They were either given bus fare or picked up and taken home by social workers. Patients were enamored with Spies. A master at charming patients, he could convince patients brought from all over the state by bus to Hillman Hospital to let him try a number of clinical investigations that might be viewed with some concern today by modern-day research committees. But Spies maintained that truly definitive answers to problems of human nutrition and metabolism could be obtained only by studies done with humans.
Although the calorie-high protein diets were beneficial in most cases of pellagra, this treatment proved impractical. It required hospitalization of severely ill pellagrins for several weeks, along with constant supervision by a physician, nurse, or dietician. In addition, hospitalization was costly. Food and treatment for the fifty test cases alone cost approximately $10,000. Furthermore, many patients after discharge were unable to buy the expensive foods necessary to protect themselves against recurrences of the disease. Thus Spies sought a cheaper method of treating pellagra.
In 1937, Dr. Conrad Elvehjem, a close personal friend and colleague of Spies, who was also professor of biochemistry at the University of Wisconsin, isolated the amide of nicotinic acid (niacin) from liver. This substance, which was originally nothing more than a "laboratory curiosity," was found to promote healing in dogs with black tongue. The effects on humans, however, had not been determined.
Spies, while working at Cincinnati General Hospital, decided to use members of his staff and himself as guinea pigs to determine what effects nicotinic acid would have on them. He administered small doses to thirteen people; three members of the staff of Cincinnati and ten non pellagrous patients were given orally an aqueous solution of nicotinic acid supplied by Eastman Kodak each day for several weeks. The dose varied in amount beginning with a few milligrams daily up to 200 milligrams daily. No serious side effects other than slight tingling and flushing of the skin were noted by the subjects. Neither did intravenous injections of nicotinic acid produce adverse reactions. After weeks of self-testing, Spies tried it on eleven pellagrins. Then on November 5, 1937 Spies reported to the Central Society for Clinical Research that patients receiving nicotinic acid showed marked improvement without any harmful effects. Similar results, which helped to confirm the safety of nicotinic acid, were observed independently by doctors at Duke University in North Carolina, at Indianapolis City Hospital in Indiana, and at an asylum and a prison in Egypt.
Next, a total of seventy-three persons with endemic pellagra were studied at the Cincinnati Hospital and at Hillman Hospital. Again, discovering that nicotinic acid was effective in treating these pellagrins and in preventing recurrences under hospital conditions, Spies directed his attention to studying its effect on adult pellagrins living at home. The habitual diet and environment of 694 pellagrins who were previously examined in Birmingham in 1936 were re-examined in 1938. Efforts were directed towards ascertaining whether they had a recurrence of pellagra and whether or not any change had been made in their dietary or economic status since 1936. Out of these pellagrins, Spies selected 199 persons in whom pellagra had occurred at least once every year for the past two to fifteen years. He then narrowed this group down to 173 people to receive nicotinic acid. After the initial examination, most of the patients returned to the clinic once a week. Each patient was treated individually and was given a weeks supply of nicotinic acid in 100 milligram tablets. The dosage was adjusted from time to time in accordance with what seemed to be the necessary amount for that individual. Patients continued to eat their unbalanced diet. Within one to three days after treatment nearly all patients responded that they felt much better and the confusion and dizziness which many experience had subsided. Of significance was the result in persons of this group who were without the drug for periods of one to two weeks. In most instances they experienced, within a week, a recurrence of their symptoms of pellagra. Spies also treated the 321 remaining pellagra cases. In many of these patients, the disease was so severe that hospitalization would have been necessary. But prompt and beneficial results were achieved with nicotinic acid therapy. Thus the use of nicotinic acid reduced the number of hospitalized pellagra cases.
Spies also studied the effects of nicotinic add on patients in mental hospitals. In severe cases of pellagra, patients were often admitted to mental institutions as psychotic. These patients often associated their skin lesions with crawling insects, worms, pain or filth. They did not respond to "psychiatric" treatment and were made worse by administering large doses of carbohydrates and medicines that were not antipellagric. With the cooperation of Drs. W. D. Partlow, W. M. Faulk, and E. L. McCafferty at the Searcy Hospital, Mt. Vernon,
Alabama and the Bryce Hospital, Tuscaloosa, Alabama, observations were made of these patients and their response to treatment with nicotinic acid.
Within twenty- four to seventy-two hours following the administration of nicotinic acid, patients became free from psychotic manifestations. This was a particularly important discovery because, until these facts were known, about twenty-five or thirty percent of all patients admitted to psychiatric hospitals in Alabama were victims of pellagra.
With the introduction of nicotinic acid, the death rate from pellagra declined dramatically. Patients brought into hospitals with a life expectancy of only a few hours were saved. "Its effect on patients, even the most severely diseased, is nothing short of miraculous,” Spies wrote Mrs. Goldberger. Three years after nicotinic acid was introduced, the death rate in 1940 was 2,040 deaths in the United States. In 1945 that figure dropped to 865.
But not all patients responded to nicotinic acid therapy. Thus what was most significant about Spies's study of nicotinic acid was his discovery of multiple vitamin deficiencies. Many patients thought to have only pellagra were actually suffering from other vitamin deficiency diseases such as beriberi, anemia, and riboflavin deficiency. The symptoms of pellagra would be relieved by administration of nicotinic acid but other deficiencies remained. For example, Spies described the case of a forty-year-old white woman who was relieved of pellagra after receiving 50 milligrams of nicotinic acid ten times a day. She returned home and continued to eat her usual inadequate diet and to take nicotinic acid. Within six weeks she developed mild peripheral neuritis; ten weeks later it became so severe she could not sleep, and her memory became impaired. Prompt relief was followed with the injection of vitamin B twice daily while she continued to eat her usual diet. This incidence indicated that only when these pellagrins were treated simultaneously with other vitamins did they have a complete remission from their deficiency diseases.
This proved to be a particularly important discovery because many physicians believed in treating nutritional diseases with single vitamins. Spies's belief that a person could have multiple nutritional deficiencies and be cured with multi-vitamin preparations earned him the appellation of a "maverick." Spies' theory ran counter to that of the editor of the Journal of the American Medical Association, Dr. Morris Fishbein, a powerful spokesman for organized medicine. Dr. Fishbein labeled Spies' approach "shotgun therapy" or "polypharmacy" and dismissed it as an absurdity. Spies battled Fishbein on this issue for many years until Spies' concept finally became medically acceptable.
The use of nicotinic acid and its amide (niacin) subsequently gained widespread acceptance in the treatment of pellagra. It proved beyond doubt that deficiency of this vitamin was the cause of pellagra. A full diet with nicotinic acid and when necessary, vitamin B, represented an advance over anything thus far offered in the treatment of pellagra.
In 1945, as pellagra began to disappear, Spies turned his attention to the undernourished children whose parents were undergoing treatment at the clinic. Frequently children came to the clinic with their parents: Spies observed that they looked listless, small, irritable, and rarely seemed interested in playing. Diet histories taken from the parents indicated that these children were not receiving sufficient nutrients to support adequate growth and development and were therefore suffering from a form of "hidden hunger.” Spies resolved to try to determine what would make the children grow normally. By studying them scientifically as they were being treated, Spies believed that he could learn the effects of poor nutrition on physical, psychological, and social development. Spies chose to experiment with the addition of milk to children's diets and determine its relationship to growth since this was an area that had received scant attention.
In 1945 he initiated a special three-year study (later extended to live years) to determine the effects of daily supplementation of a specified amount of either dry whole mild or nonfat dry milk solids on the growth process of a selected group of children. Eighty-four children (later one hundred) with histories or signs of undernourishment were selected. All children were white natives of north central Alabama. Children were paired on the basis of sex: comparative x-rays of the left hand and wrist; general body type; and apparent prevailing phase of growth. One child of each pair received the equivalent of one quart of milk every day, six days a week, for twenty months. The American Milk Institute donated dry milk solids for reconstituted use.
Five social workers, known among their colleagues as “range riders” or “bush beaters,” traveled the unpaved roads of Warrior, Leeds, Pelham, Bessemer, and Tuscaloosa, Alabama to deliver milk to the children. This was a new experience for most of the young social workers. When questioned about Spies’ attitude towards these young women traveling the country roads alone, one of them responded: “He worried some about the fact that we went out in the country, although he never felt like pampering you ... He never felt you should avoid anything because it was a risk… If you went out, you were supposed to come back with the goods.”
Everyday the social workers delivered the milk and stayed until all milk was consumed. At the same time, they noted each child's health, appetite, and spirit. They watched how a child got along with family and friends and whether he or she entered into play with the other children. Four times a year the children were brought into the hospital and carefully weighed, measured, and x- rayed. Different methods such as height/weight graphs, photographs showing physical development, and x-rays were used to measure and correlate the growth and development of each child. Results of this five-year study showed remarkable improvements in the children's physical growth and strength as well as learning ability. What was most significant about this study was that no one prior to this had demonstrated specifically just what a measured quantity of milk could do for children who had subsisted on an inadequate diet.
By the 1940's, the clinic had grown from its modest beginnings in a hallway at Hillman Hospital to occupy the second, fourth, and fifth floors of the Hillman Outpatient Clinic. Rather than a staff of three, Spies now surrounded himself with a staff of forty bright young men and women. Funding for the clinic was always a problem since the city of Birmingham and Jefferson County were never charged for patient care and expenses. To obtain funds, Spies had to travel extensively to promote his nutrition clinic. He received national attention from newspapers and from his "unofficial publicity agent," Dr. Paul de Kruif, whose book Life Among the Doctors, helped promote Spies' work in Birmingham. The University of Cincinnati financed the clinic the first year in 1937; subsequent seasons were financed by philanthropic foundations such as the Rockefeller Foundation, the Macy Fund, and the Markle Foundation. Spies resisted the temptation to use government funds. As former associate Dr. Samuel Dreizen recalls: "Instead he preferred the freedom of thought and action afforded by support from interested segments of the private sector. He was a salesman for medical research long before it became fashionable and plentiful."
In addition to philanthropic support, a large portion of Spies's funds came from industry. Spies maintained that the productivity of industry was directly related to the nutritional state of its employees; therefore, industry stood to benefit from every advance made in the science of nutrition. Industrialists, he felt, had a moral obligation to support nutritional and medical research. This concept helped Spies cultivate the friendship and financial support of local as well as national leaders of industry, a particularly important development at a time when the federal government did not provide funds for research.
These leaders of industry formed themselves into a committee called the Spies Committee for Clinical Research. The committee had thirty-nine directors plus a scientific consulting subcommittee of nine members, five of whom have been presidents of American Institute of Nutrition. Its directors, by contrast, had access to money or public opinion or were executives of large companies, especially in the pharmaceutical and food industry. Some of the biggest names in industry, such as Dr. Charles F. Kettering, director of General Motors; John H. Kraft, president of Kraft Food Company; C. M. White, president of Republic Steel Corporation; and August A. Busch, Jr., president of Anheuser Busch, Inc., supported this committee. In addition to a national committee, prominent Birmingham industrialists organized a local committee in the 1940's to support Spies's work. Headed by Thomas Bragg, vice-president of Alabama Power, J. W. Porter, president of Alabama By-Products Corporation, and R. H. Wharton, county commissioner, this Birmingham group successfully raised $15,000 to buy new laboratory equipment for the nutrition clinic.
After pellagra and other vitamin deficiency diseases had declined around 1945, welfare agencies and doctors still referred a number of malnourished patients to Spies. Many of those were thought to have primary vitamin deficiencies. But Spies and his staff determined that these disturbances in nutrition were secondary to chronic disease such as diabetes, cancer, or tuberculosis. Spies then devoted the last fifteen years, prior to his death, to studying the effects of chronic diseases on the nutritional status of the individual. Before his death in 1960, Spies was recognized as the authority among researchers in fighting "hidden hunger" and starvation throughout the world. Spies helped define the role of vitamins in human nutrition and perhaps more than any other person contributed to their general clinical application.
Summary
Spies received recognition for his work in eliminating various aspects of "hidden hunger" - pellagra in the American South, sprue in the tropics, and undernutrition in north central Alabama children. Spies spent over thirty years studying nutrition and its effects on individuals. He had a theory that all nutritional diseases were caused by chemical "lacks" in the body, which could be made up for by doses of vitamins and minerals. He proved this theory with his treatment of pellagra with vitamins.
Although Spies made a number of nutritional discoveries in his clinic, he is most noted for his work in eradicating pellagra in the South. Spies built on the work of Dr. Joseph Goldberger, who had demonstrated in 1916 and 1920, that the absence of certain factors from the diet played a major role in the causation of pellagra. Goldberger reduced the frequency of occurrence of the disease by adding certain foods - high in the so-called pellagra-preventive factor - to a deficient diet.
Yet in spite of diets constructed according to Goldberger's suggestions there was little reduction in the mortality rate of advanced cases of pellagra. At least one out of three persons with pellagra died before 1940. In addition to the high death rate, other problems existed in treating pellagrins. First hospitalization of severely ill pellagrins was expensive. Food and treatment for the fifty test cases alone in 1936 cost approximately $10,000. Secondly, many patients after discharge were unable to buy the expensive foods necessary to protect themselves against recurrences of the disease. Spies therefore sought a successful yet inexpensive treatment for pellagra.
In 1937, he began experimenting with a new substance called nicotinic acid which had been proven safe on dogs with black tongue by Dr. Conrad Elvehjem. Because of the paucity of literature on nicotinic acid and its effects on humans, Spies decided to use members of his staff and himself as guinea pigs to determine what effects (if any) nicotinic acid would have on them. He administered small doses to thirteen people. The dosage varied from a few milligrams to two hundred per day. No serious side effects other than slight tingling and flushing of the skin were noted by the subjects. Neither did intravenous injections of nicotinic acid produce adverse reactions. After trying it on eleven pellagrins, whose symptoms cleared up within 24 to 72 hours, Spies reported to the Central Society for Clinical Research on November 5, 1937 that patients receiving nicotinic acid showed marked improvement without any harmful effects.
Nicotinic acid proved to be an inexpensive and safe cure for pellagra. Patients did not have to remain in the hospital. They could receive nicotinic acid in tablet form to take by mouth and return to the nutrition clinic for periodic checkups. With the introduction of nicotinic acid, the death rate from pellagra declined dramatically. Three years after nicotinic acid was introduced, the death rate in 1940 was 2,040 deaths in the United States. In 1945 that figure dropped to 865.
Yet not every patient had a complete remission from this therapy. And his greatest impact in working with pellagra lay in the recognition that, although nicotinic acid could cure symptoms of pellagra, multi-vitamins were necessary when patients exhibited several other nutritional deficiencies at the same time. Spies' work helped to convince the medical profession and general public the importance of nutrition and the role of vitamins in the cure of deficiency diseases.
One of Spies' lasting contributions to the eradication of deficiency diseases was his involvement in fostering and promoting state and federal laws in the 1940’s, laws that required manufacturers to enrich cereal and dairy products with synthetic vitamins, thereby helping to provide a partial shield against pellagra and other nutritional deficiencies.
Certainly other factors led to the defeat of pellagra: the rapid urbanization of the South after World War II, better living standards, advances in technology, new methods of preserving foods, and higher wages. But a significant contribution in the late 1930's in Birmingham, Alabama by Tom Douglas Spies with diet, vitamins, and nicotinic acid, helped finally pave the way for the conquest of "hidden hunger" in the American South.

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Transcript

PREFACE The study of health in the history of Jefferson County, Alabama illuminates the structure and values of our society as well as the nature of medicine and the health sciences. The collection of the documents of this exciting history is the mission of the JCMS/UAB Health Sciences Archives; and this paper, the first in a series of Occasional Papers, is a logical product of the collecting and curating activity. In addition to collection development, the Archives engages in public outreach activities such as traveling historical displays, an audio-visual production and oral history projects. Oral history preserves the recollections of people who have participated in and witnessed the making of history – in this case the histories of our hospitals, medical schools, private practices and public institutions. Subsequent issues in the Occasional Paper series will present stimulating extracts from the oral history projects. The author of this paper, Linda Casselman Akenhead, is a product of the graduate history program of the University of Alabama at Birmingham, and her research on Dr. Tom Douglas Spies originated under the direction of Professor Virginia Van der Veer Hamilton. Ms. Akenhead's interest in the history of medicine and nutrition in particular is grounded in her past experience as a clinical dietician. She also served as a member of the JCMS Archives Committee and researched the history of medicine in Jefferson County for the Archives' audiovisual production. The JCMS/UAB Health Sciences Archives thanks Dean James A. Pitman, Jr., M.D., for his support of the Archives, especially the Occasional Papers project. Virginia Fisher Archivist In the American South of the early twentieth century, pellagra symbolized poverty. Frequently referred to as the "scourge" or "lazy" disease by the Northern press, pellagra afflicted sharecroppers and tenant farmers as well as mill and mine workers. Low income farmers and working people could not afford expensive perishable food; therefore, these men, women, and children existed on relatively cheap food items available through a company commissary or rural grocery store such as cornmeal, molasses, salt pork, and dried beans. Depression gripped the South in the 1920's, resulting in a Public Health Service prediction that collapse of the cotton market would result in an increase of pellagra cases. A storm of objections from Southern politicians, businessmen, and physicians met this announcement; because pellagra was a symbol of poverty, these leaders denied that the South was a victim of widespread "hidden hunger." Yet pellagra afflicted thousands of people in the area; not until 1945 were most vestiges of the disease eradicated from the South. In part, the eradication of pellagra was due to the disappearance of company owned mill towns and the disappearance of cotton tenantry. However, a major breakthrough in the conquest of pellagra is attributed to the successful experimentation of Dr. Tom Spies during the late 1930’s with the use of nicotinic acid in treating pellagra at the nutrition clinic in Hillman Hospital-- now a part of the Medical Center of the University of Alabama at Birmingham. Interestingly, pellagra was first identified as endemic in Alabama in 1906; it was also in this state that the work of Dr. Tom Douglas Spies contributed to the successful eradication of the disease. Spies (rhymes with "fees") was born September 21, 1902 in Ravenna, Texas. He received his B.A. from the University of Texas in 1923 and his M.D. from Harvard Medical School in 1927. He came to Alabama in 1936 at the invitation of Dr. J. S. McLester, Physician-in-Chief of Hillman Hospital, and remained in Birmingham almost a quarter of a century. Spies held five teaching positions, was affiliated with many medical organizations, wrote a number of major articles and texts, and received plaudits from a number of organizations both local and international. Spies first became aware of pellagra as a child when he joined his two physician uncles on rounds to the homes of ranchers and farmers in an area called Red River Valley in Texas. He was troubled by his uncles' inability to cure the disease. Later in 1930, as an intern at Lakeside Hospital in Cleveland, Ohio, he treated his first pellagra patient. Although Spies administered the Goldberger diet - the recommended therapy of that time- the patient died. He blamed this failure on the fact that his patient did not eat enough food. After reviewing the hospital records of patients with pellagra, he discovered that 54% of all patients afflicted with the disease died. Spies set out to find the cure for pellagra. This determination provided the treatment that would finally eradicate pellagra. Unmarried - although he claimed to be married to his work - and having few interests outside of medicine, Spies concentrated on his medical research. Friends adored him and used such terms as "gentle" and "magnanimous" to describe Spies's personality. He considered his employees as “family” and frequently entertained them with dinners at the local country club. It was not unusual for them to receive a thank-you note or birthday card from Spies. He had a knack for remembering names and dates. He was not a church-goer, claiming that he could accomplish more for the human race by spending his time in his clinic rather than in church. One of Spies's former associates, Dr. Hady Lopez, described Spies as "an independent man who made his decisions acting on his own and with the intellectual capacity to direct others in carrying out his wishes.” Spies devoted his life to advancing the science of nutrition. He is credited with a number or discoveries at this nutrition clinic in Birmingham: among these are the use of synthetic folic acid for pernicious anemia; the use or riboflavin for diseases of the eye; and the use of thiamin for beriberi and heart disease. But he is most noted for his successful Alabama experiments with nicotinic acid in the treatment and prevention of pellagra. In order to understand the importance of Spies' work with pellagra, a brief summary of the disease is helpful. Pellagra is caused by a deficiency of niacin which is one of the B-complex vitamins. Niacin is synthesized in the human from the amino acid tryptophan and therefore is an anti-pellagra factor. Foods such as milk and meat are good sources of tryptophan which occurs in crude protein. Corn, however, in addition to being deficient in niacin, is also deficient in tryptophan. People whose diet centers around corn are therefore pellagra prone. Characteristics of the disease include symptoms of dermatitis, anorexia, weakness, diarrhea. The tongue becomes thickly coated and the mouth extremely sore. Mental changes such as confusion, loss of memory, depression, and delirium may occur in more advanced cases. Pellagra did not respect age, sex, or race. A marked feature of the disease was the seasonal prevalence in the spring following the restricted and inadequate diet through the winter months. To explain this mysterious disease, early medical researchers advanced a number of theories. The most widely accepted theory attributed pellagra to corn since this was the major dietary staple in districts with endemic pellagra in Italy during the nineteenth century. In 1872, Cesare Lombroso, an Italian physician, attributed pellagra to a toxin or bacteria on spoiled corn; this theory remained popular for many years. In 1911, the Illinois Pellagra Commission concluded that the primary etiological factor was a living micro-organism of unknown nature, the probable source of infection being through the intestinal tract. Early treatments for pellagra included transfusions of blood from recovered pellagrins; large doses of castor oil; static electricity; or - for those who could afford it – a trip to the healing waters of mineral springs. In 1906, the first signs of endemic pellagra in the United States were discovered by Alabama's Dr. George Searcy who recognized pellagra in patients at the Hospital for the Colored Insane at Mount Vernon, Alabama. It was the same disease that had occurred or reappeared in a few patients at Mount Vernon every year since 1901. In his 1908 address to the Medical Association of the State of Alabama, Dr. Searcy noted that during the summer of 1906, there were eighty-eight cases of pellagra, with a mortality rate of sixty-four percent at the Mount Vernon Hospital. The average age of the patients was thirty- four years; two-thirds of these had been in the hospital longer than one year. In trying to determine the cause of pellagra, Dr. Searcy noticed that not one of the hospital staff members had any symptoms of the disease. Comparing the diets of staff members and patients, he observed that patients received damaged corn with their meals. He sent a sample of the corn to Washington, D.C. where it was pronounced unfit for human consumption. Dr. Searcy removed the damaged corn and grits from the patients' diets, substituting wheat bread and potatoes. Within ten days no new cases appeared. Armed with this knowledge, Dr. Searcy warned other physicians to be alert for signs for pellagra because much of the 1905 Western corn crop had been damaged by wet weather. Following Dr. Searcy's warning, Southern doctors reported nine cases of pellagra at the State Hospital for the Insane at Columbia, South Carolina, and forty cases of pellagra resulting in twenty-three deaths at the Georgia State Sanitarium in Milledgeville. Although Dr. Searcy's discovery helped physicians become aware that pellagra existed in the United States, it still did not solve the problem of how to treat it. Pellagra was now appearing in more Southern states than in any other section or the country. According to the 1912 Surgeon General's Report on the geographical distribution of pellagra in the United States, the lower Southern states were at a higher risk for pellagra outbreaks. In Alabama alone, the two counties with the highest incidence of pellagra were Jefferson, reporting 225 cases of pellagra, and Clark, reporting 155 cases. Dr. Lewis Coleman Morris of Birmingham, in an annual address to the Southern Medical Association in 1912, noted that “despite all or our efforts up to this time the prevent ion of this disease remains obscure.” By 1913 the total number of deaths from pellagra in Alabama alone exceeded 500 cases, and the disease now ranked behind tuberculosis, pneumonia, and typhoid fever as causing the greatest number or deaths from infectious disease in the state. Fear that the disease was communicable led to drastic measures of isolation and quarantine. The Alabama State Board of Health, for example, issued a recommendation that pellagrins be "thoroughly isolated in reference to clothing, bedding, and the use of crockery." Several factors contributed to the rise of pellagra in the South. The crop-lien system imposed a vicious cycle on Southern agriculture. To repay loans, many farmers had to plant their land with the most marketable cash crop - cotton. The lower the price of cotton, the more a farmer had to plant in order to meet his debts. This reduced the amount of land devoted to food crops and animals. Farmers who might otherwise have produced their own food became more dependent on merchants for their supplies. Since they were forced to rely on market prices, cotton futures, and credits, sharecroppers and tenant farmers were unable to afford expensive perishable foods. In addition, the change in the character of the corn meal contributed to the rise in pellagra. Before 1900, most meal used in smaller towns and practically all consumed in rural areas was ground by small local grist mills. At the turn of the century finely bolted meal produced by large milling companies appeared. This so-called Western meal was thoroughly degerminated to prevent rancidity during storage and shipment. This resulted in all essentially vitamin-free product. Within a few years, the corn meal and other staple cereal foods of millions of people changed from what was essentially a vitamin-rich whole grain product to a highly refined carbohydrate that contained practically no essential vitamins or other nutrients. Finally in 1915, an early breakthrough in the etiology of the disease was announced at the National Pellagra Conference in Columbia, South Carolina. According to Dr. Joseph Goldberger, "an unbalanced diet has been fully and scientifically demonstrated to be the cause of pellagra and the disease has been cured by changing the diet to include peas, beans, and milk.” Goldberger began his study of pellagra in 1914 when the Public Health Service placed him in charge of identifying its causes. Goldberger made repeated trips throughout the South visiting mental hospitals and orphan asylums in Georgia, Alabama, Florida, Kentucky, and Mississippi where pellagra was most prevalent. Goldberger checked the diet of each patient and found that they lacked sufficient amounts of eggs, milk, and meat. He noticed that the high carbohydrate content of the diets came from cornmeal, white flour, sugar molasses, fat pork, and polished rice. In order to test the theory that pellagra was caused by a faulty diet, and not by an infection as many medical doctors assumed, Goldberger and his wife ingested or injected samples of effluvia from very ill victims of pellagra. Having found no infection, he returned to his study of diet. This time he induced pellagra on healthy white male convicts at the Rankin farm of the Mississippi State Penitentiary by feeding the same monotonous, principally cereal diet, which he had found in orphanages and mental hospitals. This experiment reinforced his belief that pellagra resulted from a dietary deficiency in certain classes or food. But a large portion of Southern medical professionals were reluctant to accept the Goldberger "diet theory" as the only etiological factor in pellagra. The idea that a disease was brought on by something "you did not eat" was unheard of at this time. Undaunted, Goldberger continued his studies – this time in seven South Carolina mill villages. From April 1916 to December 1916, Goldberger carried on a bi-weekly house-to-house search for cases of pellagra. Comparing the diets of families with pellagra and those without the disease revealed that the latter consumed a more liberal supply of animal protein foods (lean meat, milk, cheese. and eggs). Goldberger then drew a correlation between diet and economics. In general, as income fell, the incidence of the disease rose and showed an increasing tendency to affect members of the same family. Goldberger again reiterated that a faulty or unbalanced diet resulted in pellagra. Goldberger had not publicly announced his mill village findings until the summer of 1921 when economic prosperity began to decline. He sent a letter to the Public Health Service headquarters in Washington stating: "For all practical purposes we have in our own country this summer thousands of people who are starving and dying ... We are feeding the Near East and the Far East but we are neglecting our own people here at home.” The Public Health Service joined Goldberger in announcing that an epidemic of pellagra among farmers forced into starvation diets would occur due to the collapse of the cotton market and the "ravages" of the boll weevil. A storm of objections and abuse met this announcement. Local public health officials denied that there was "hidden hunger" in the South. Birmingham physician, Dr. Seale Harris, wrote an editorial to the Southern Medical Association criticizing the unfavorable publicity the South had received because of pellagra. Harris declared, in part: "Zealots of food deficiency as the sole cause of pellagra… had missed their mark and left the impression that the South is backward and poverty stricken. They have exaggerated the seriousness of pellagra as a disease.” He further elaborated that this has interfered with the "agricultural development of the most fertile lands in the United States, and it has prevented many industries from locating in the favored South.” Southern political leaders also denied that pellagra was increasing as did many health departments in Tennessee, Louisiana, Alabama, North Carolina, Virginia, and Georgia. But most state health officers did not know the extent of the pellagra situation in their state since pellagra was not always a reportable disease. Also many business and political leaders denied the existence of a pellagra problem. They rejected Goldberger's efforts to tie pellagra to the basic poverty of the South because they were unwilling to admit that the South was poor. Finally, many Southern physicians rejected Goldberger's findings because they felt nutrition was an area of science suitable for study by chemists, not physicians. Because they were schooled in the bacteriological concept of disease, many doctors found it difficult to accept Goldberger's findings. But Goldberger continued his study of pellagra until 1929 when cancer cut short his career. Pellagra continued to leave its mark on the South into the 1930's. Between 1920-1935, 58 out of 183 pellagra patients admitted to Birmingham's Hillman Hospital died from pellagra. Although these patients had received the Goldberger diet, the death rate had not diminished. Despite the interest in pellagra since the early 1900's, physicians were unable to affect the ultimate outcome of severe cases. There was a consistent death rate of one in two to four hospitalized cases. Dr. James L. McLester, physician-in-chief at Hillman Hospital, had read a 1934 study by Spies describing how he had reduced the mortality rate from 54% to 6% in a series of 125 cases of severely diseased pellagra patients at Lakeside Hospital in Cleveland, Ohio. These cases consisted largely of derelicts, chiefly alcoholics with pellagra, and patients with the disease secondary to other organic conditions. Spies was experimenting with these patients to see if alcohol was a primary factor in the cause of pellagra. He took the derelicts and fed them the Goldberger diet; however, at the same time he allowed them to consume as much corn liquor as they could drink. The pellagra cleared up, indicating that it had not been caused solely by alcohol but by the absence of essential food factors. When he reported the results of his study on the alcoholics to medical conventions and journals, some physicians questioned whether or not his findings would apply to the nutritional status of the people living in the South who were not alcoholics. Spies maintained that pellagra in the South would respond to a similar therapy. Still skeptical, McLester invited Spies to come to Birmingham to prove whether he could keep “doomed pellagrins out of the grave in the South.” Spies accepted the challenge and selected three people to come with him to Birmingham: a dietician, Jean Grant; a nurse, Ann Van Blaricom; and a medical assistant, Dr. Austin Chinn. Since conditions in the Hillman were very crowded when Spies arrived, he was offered the only space available for carrying out his studies - a hallway which would later become the Hillman Emergency Clinic. During the spring and summer of 1936, Spies tested his feeding regime on fifty critically ill pellagra patients. The treatment consisted of complete bed rest plus very high caloric, high protein diets, with much larger quantities of brewer's yeast and liver than had been used before. When possible, patients consumed approximately 4,000 to 5,000 calories daily with 125 to 130 grams of protein. Each patient received individual attention and dose observation during the experiment. Patients were required to eat all their meals. Substitutions in form and consistency of foods were made when patients had difficulty consuming a regular diet. It often took an hour to force a meal down and see that it stayed down. Sometimes Spies, Grant, or Chinn took twelve hour shifts with the patients seeing that all food was consumed. Brewer's yeast was used as the specific therapeutic agent in those patients who were not vomiting. It was usually given in one-ounce doses mixed in eggnog three or more times daily. When vomiting or diarrhea was present, liver extract – a relatively new method in treating pellagra – was given intravenously in the severest cases, intramuscular in others, every two to three hours to those too sick to eat. Only three patients out of fifty failed to respond to this treatment. Spies's successful study indicated that pellagra was due to deficiencies in the diet and that there was no difference in response of patients with pellagra in the North or South. But news of his achievements did not impress some medical doctors in the South. They still insisted that endemic pellagra was not the same as the mild Northern variety "caused by alcohol." Yet Spies remained adamant: the irritability, dizziness, and tired feeling of which many pellagra patients complained was due to the "hunger sickness" that gave the South its reputation of being "lazy." Although Spies came to Birmingham in the early 1930's with the idea of staying only long enough to complete one brief study on pellagra, he found the wealth of clinical material at the Hillman Hospital and Birmingham area conducive to further studies. The staff of Hillman Hospital invited Spies to remain in Birmingham. Following his acceptance, the Department of Internal Medicine of the University of Cincinnati opened a nutrition clinic at Hillman Hospital in 1937, and granted Spies a yearly nine month's leave-of-absence to work in Birmingham. Spies declared that “other hospitals would have been available for studies but that Hillman was chosen because of the fine spirit of cooperation and the high standards of the staff.” When the clinic opened, Spies soon realized that pellagra was not confined within the city limits. Mining villages, camps, and tenant farmers were located outside the city limits. Large numbers of these people had been out of work during the Depression. Many were ill and did not have the strength, energy, nor money to seek assistance. Thus Spies chose to attack pellagra aggressively. Rather than wait for pellagrins to come to Hillman, he and his staff would drive the country roads to Jefferson and neighboring counties looking for victims of the disease. They would seek out the tenant, sharecropper, or mill family. Since the early stages of pellagra were sometimes difficult to identify, Spies' "clinical test" to determine pellagra was to look at the family dog. Pets, eating scraps from the tables of persons who ate a pellagra-producing diet, tended to develop black tongue (a disease analogous to pellagra in humans). This observation provided Spies with a reliable indicator that family members would be afflicted with pellagra. Because of his warm and friendly attitude towards these people, Spies gained acceptance into their homes. When symptoms of pellagra were found in a family, Spies often brought them back to Hillman for treatment. Those with advanced cases remained in the hospital. Detailed diet and social histories were obtained. Diet histories of all families generally revealed a high carbohydrate and low protein diet consisting of fatback, always cornbread, a few greens for those who could afford a small garden, molasses, and alcohol for those who had a still. As patients began to improve, staff members counseled them on how to diversify their diets. Word got around about the nutrition clinic and patients began to seek treatment. Free transportation provided the incentive to get patients to come to the clinic for treatment. They were either given bus fare or picked up and taken home by social workers. Patients were enamored with Spies. A master at charming patients, he could convince patients brought from all over the state by bus to Hillman Hospital to let him try a number of clinical investigations that might be viewed with some concern today by modern-day research committees. But Spies maintained that truly definitive answers to problems of human nutrition and metabolism could be obtained only by studies done with humans. Although the calorie-high protein diets were beneficial in most cases of pellagra, this treatment proved impractical. It required hospitalization of severely ill pellagrins for several weeks, along with constant supervision by a physician, nurse, or dietician. In addition, hospitalization was costly. Food and treatment for the fifty test cases alone cost approximately $10,000. Furthermore, many patients after discharge were unable to buy the expensive foods necessary to protect themselves against recurrences of the disease. Thus Spies sought a cheaper method of treating pellagra. In 1937, Dr. Conrad Elvehjem, a close personal friend and colleague of Spies, who was also professor of biochemistry at the University of Wisconsin, isolated the amide of nicotinic acid (niacin) from liver. This substance, which was originally nothing more than a "laboratory curiosity" was found to promote healing in dogs with black tongue. The effects on humans, however, had not been determined. Spies, while working at Cincinnati General Hospital, decided to use members of his staff and himself as guinea pigs to determine what effects nicotinic acid would have on them. He administered small doses to thirteen people; three members of the staff of Cincinnati and ten non pellagrous patients were given orally an aqueous solution of nicotinic acid supplied by Eastman Kodak each day for several weeks. The dose varied in amount beginning with a few milligrams daily up to 200 milligrams daily. No serious side effects other than slight tingling and flushing of the skin were noted by the subjects. Neither did intravenous injections of nicotinic acid produce adverse reactions. After weeks of self-testing, Spies tried it on eleven pellagrins. Then on November 5, 1937 Spies reported to the Central Society for Clinical Research that patients receiving nicotinic acid showed marked improvement without any harmful effects. Similar results, which helped to confirm the safety of nicotinic acid, were observed independently by doctors at Duke University in North Carolina, at Indianapolis City Hospital in Indiana, and at an asylum and a prison in Egypt. Next, a total of seventy-three persons with endemic pellagra were studied at the Cincinnati Hospital and at Hillman Hospital. Again, discovering that nicotinic acid was effective in treating these pellagrins and in preventing recurrences under hospital conditions, Spies directed his attention to studying its effect on adult pellagrins living at home. The habitual diet and environment of 694 pellagrins who were previously examined in Birmingham in 1936 were re-examined in 1938. Efforts were directed towards ascertaining whether they had a recurrence of pellagra and whether or not any change had been made in their dietary or economic status since 1936. Out of these pellagrins, Spies selected 199 persons in whom pellagra had occurred at least once every year for the past two to fifteen years. He then narrowed this group down to 173 people to receive nicotinic acid. After the initial examination, most of the patients returned to the clinic once a week. Each patient was treated individually and was given a weeks supply of nicotinic acid in 100 milligram tablets. The dosage was adjusted from time to time in accordance with what seemed to be the necessary amount for that individual. Patients continued to eat their unbalanced diet. Within one to three days after treatment nearly all patients responded that they felt much better and the confusion and dizziness which many experience had subsided. Of significance was the result in persons of this group who were without the drug for periods of one to two weeks. In most instances they experienced, within a week, a recurrence of their symptoms of pellagra. Spies also treated the 321 remaining pellagra cases. In many of these patients, the disease was so severe that hospitalization would have been necessary. But prompt and beneficial results were achieved with nicotinic acid therapy. Thus the use of nicotinic acid reduced the number of hospitalized pellagra cases. Spies also studied the effects of nicotinic add on patients in mental hospitals. In severe cases of pellagra, patients were often admitted to mental institutions as psychotic. These patients often associated their skin lesions with crawling insects, worms, pain or filth. They did not respond to "psychiatric" treatment and were made worse by administering large doses of carbohydrates and medicines that were not antipellagric. With the cooperation of Drs. W. D. Partlow, W. M. Faulk, and E. L. McCafferty at the Searcy Hospital, Mt. Vernon, Alabama and the Bryce Hospital, Tuscaloosa, Alabama, observations were made of these patients and their response to treatment with nicotinic acid. Within twenty- four to seventy-two hours following the administration of nicotinic acid, patients became free from psychotic manifestations. This was a particularly important discovery because, until these facts were known, about twenty-five or thirty percent of all patients admitted to psychiatric hospitals in Alabama were victims of pellagra. With the introduction of nicotinic acid, the death rate from pellagra declined dramatically. Patients brought into hospitals with a life expectancy of only a few hours were saved. "Its effect on patients, even the most severely diseased, is nothing short of miraculous,” Spies wrote Mrs. Goldberger. Three years after nicotinic acid was introduced, the death rate in 1940 was 2,040 deaths in the United States. In 1945 that figure dropped to 865. But not all patients responded to nicotinic acid therapy. Thus what was most significant about Spies's study of nicotinic acid was his discovery of multiple vitamin deficiencies. Many patients thought to have only pellagra were actually suffering from other vitamin deficiency diseases such as beriberi, anemia, and riboflavin deficiency. The symptoms of pellagra would be relieved by administration of nicotinic acid but other deficiencies remained. For example, Spies described the case of a forty-year-old white woman who was relieved of pellagra after receiving 50 milligrams of nicotinic acid ten times a day. She returned home and continued to eat her usual inadequate diet and to take nicotinic acid. Within six weeks she developed mild peripheral neuritis; ten weeks later it became so severe she could not sleep, and her memory became impaired. Prompt relief was followed with the injection of vitamin B twice daily while she continued to eat her usual diet. This incidence indicated that only when these pellagrins were treated simultaneously with other vitamins did they have a complete remission from their deficiency diseases. This proved to be a particularly important discovery because many physicians believed in treating nutritional diseases with single vitamins. Spies's belief that a person could have multiple nutritional deficiencies and be cured with multi-vitamin preparations earned him the appellation of a "maverick." Spies' theory ran counter to that of the editor of the Journal of the American Medical Association, Dr. Morris Fishbein, a powerful spokesman for organized medicine. Dr. Fishbein labeled Spies' approach "shotgun therapy" or "polypharmacy" and dismissed it as an absurdity. Spies battled Fishbein on this issue for many years until Spies' concept finally became medically acceptable. The use of nicotinic acid and its amide (niacin) subsequently gained widespread acceptance in the treatment of pellagra. It proved beyond doubt that deficiency of this vitamin was the cause of pellagra. A full diet with nicotinic acid and when necessary, vitamin B, represented an advance over anything thus far offered in the treatment of pellagra. In 1945, as pellagra began to disappear, Spies turned his attention to the undernourished children whose parents were undergoing treatment at the clinic. Frequently children came to the clinic with their parents: Spies observed that they looked listless, small, irritable, and rarely seemed interested in playing. Diet histories taken from the parents indicated that these children were not receiving sufficient nutrients to support adequate growth and development and were therefore suffering from a form of "hidden hunger.” Spies resolved to try to determine what would make the children grow normally. By studying them scientifically as they were being treated, Spies believed that he could learn the effects of poor nutrition on physical, psychological, and social development. Spies chose to experiment with the addition of milk to children's diets and determine its relationship to growth since this was an area that had received scant attention. In 1945 he initiated a special three-year study (later extended to live years) to determine the effects of daily supplementation of a specified amount of either dry whole mild or nonfat dry milk solids on the growth process of a selected group of children. Eighty-four children (later one hundred) with histories or signs of undernourishment were selected. All children were white natives of north central Alabama. Children were paired on the basis of sex: comparative x-rays of the left hand and wrist; general body type; and apparent prevailing phase of growth. One child of each pair received the equivalent of one quart of milk every day, six days a week, for twenty months. The American Milk Institute donated dry milk solids for reconstituted use. Five social workers, known among their colleagues as “range riders” or “bush beaters,” traveled the unpaved roads of Warrior, Leeds, Pelham, Bessemer, and Tuscaloosa, Alabama to deliver milk to the children. This was a new experience for most of the young social workers. When questioned about Spies’ attitude towards these young women traveling the country roads alone, one of them responded: “He worried some about the fact that we went out in the country, although he never felt like pampering you ... He never felt you should avoid anything because it was a risk… If you went out, you were supposed to come back with the goods.” Everyday the social workers delivered the milk and stayed until all milk was consumed. At the same time, they noted each child's health, appetite, and spirit. They watched how a child got along with family and friends and whether he or she entered into play with the other children. Four times a year the children were brought into the hospital and carefully weighed, measured, and x- rayed. Different methods such as height/weight graphs, photographs showing physical development, and x-rays were used to measure and correlate the growth and development of each child. Results of this five-year study showed remarkable improvements in the children's physical growth and strength as well as learning ability. What was most significant about this study was that no one prior to this had demonstrated specifically just what a measured quantity of milk could do for children who had subsisted on an inadequate diet. By the 1940's, the clinic had grown from its modest beginnings in a hallway at Hillman Hospital to occupy the second, fourth, and fifth floors of the Hillman Outpatient Clinic. Rather than a staff of three, Spies now surrounded himself with a staff of forty bright young men and women. Funding for the clinic was always a problem since the city of Birmingham and Jefferson County were never charged for patient care and expenses. To obtain funds, Spies had to travel extensively to promote his nutrition clinic. He received national attention from newspapers and from his "unofficial publicity agent" Dr. Paul de Kruif, whose book Life Among the Doctors, helped promote Spies' work in Birmingham. The University of Cincinnati financed the clinic the first year in 1937; subsequent seasons were financed by philanthropic foundations such as the Rockefeller Foundation, the Macy Fund, and the Markle Foundation. Spies resisted the temptation to use government funds. As former associate Dr. Samuel Dreizen recalls: "Instead he preferred the freedom of thought and action afforded by support from interested segments of the private sector. He was a salesman for medical research long before it became fashionable and plentiful." In addition to philanthropic support, a large portion of Spies's funds came from industry. Spies maintained that the productivity of industry was directly related to the nutritional state of its employees; therefore, industry stood to benefit from every advance made in the science of nutrition. Industrialists, he felt, had a moral obligation to support nutritional and medical research. This concept helped Spies cultivate the friendship and financial support of local as well as national leaders of industry, a particularly important development at a time when the federal government did not provide funds for research. These leaders of industry formed themselves into a committee called the Spies Committee for Clinical Research. The committee had thirty-nine directors plus a scientific consulting subcommittee of nine members, five of whom have been presidents of American Institute of Nutrition. Its directors, by contrast, had access to money or public opinion or were executives of large companies, especially in the pharmaceutical and food industry. Some of the biggest names in industry, such as Dr. Charles F. Kettering, director of General Motors; John H. Kraft, president of Kraft Food Company; C. M. White, president of Republic Steel Corporation; and August A. Busch, Jr., president of Anheuser Busch, Inc., supported this committee. In addition to a national committee, prominent Birmingham industrialists organized a local committee in the 1940's to support Spies's work. Headed by Thomas Bragg, vice-president of Alabama Power, J. W. Porter, president of Alabama By-Products Corporation, and R. H. Wharton, county commissioner, this Birmingham group successfully raised $15,000 to buy new laboratory equipment for the nutrition clinic. After pellagra and other vitamin deficiency diseases had declined around 1945, welfare agencies and doctors still referred a number of malnourished patients to Spies. Many of those were thought to have primary vitamin deficiencies. But Spies and his staff determined that these disturbances in nutrition were secondary to chronic disease such as diabetes, cancer, or tuberculosis. Spies then devoted the last fifteen years, prior to his death, to studying the effects of chronic diseases on the nutritional status of the individual. Before his death in 1960, Spies was recognized as the authority among researchers in fighting "hidden hunger" and starvation throughout the world. Spies helped define the role of vitamins in human nutrition and perhaps more than any other person contributed to their general clinical application. Summary Spies received recognition for his work in eliminating various aspects of "hidden hunger" - pellagra in the American South, sprue in the tropics, and undernutrition in north central Alabama children. Spies spent over thirty years studying nutrition and its effects on individuals. He had a theory that all nutritional diseases were caused by chemical "lacks" in the body, which could be made up for by doses of vitamins and minerals. He proved this theory with his treatment of pellagra with vitamins. Although Spies made a number of nutritional discoveries in his clinic, he is most noted for his work in eradicating pellagra in the South. Spies built on the work of Dr. Joseph Goldberger, who had demonstrated in 1916 and 1920, that the absence of certain factors from the diet played a major role in the causation of pellagra. Goldberger reduced the frequency of occurrence of the disease by adding certain foods - high in the so-called pellagra-preventive factor - to a deficient diet. Yet in spite of diets constructed according to Goldberger's suggestions there was little reduction in the mortality rate of advanced cases of pellagra. At least one out of three persons with pellagra died before 1940. In addition to the high death rate, other problems existed in treating pellagrins. First hospitalization of severely ill pellagrins was expensive. Food and treatment for the fifty test cases alone in 1936 cost approximately $10,000. Secondly, many patients after discharge were unable to buy the expensive foods necessary to protect themselves against recurrences of the disease. Spies therefore sought a successful yet inexpensive treatment for pellagra. In 1937, he began experimenting with a new substance called nicotinic acid which had been proven safe on dogs with black tongue by Dr. Conrad Elvehjem. Because of the paucity of literature on nicotinic acid and its effects on humans, Spies decided to use members of his staff and himself as guinea pigs to determine what effects (if any) nicotinic acid would have on them. He administered small doses to thirteen people. The dosage varied from a few milligrams to two hundred per day. No serious side effects other than slight tingling and flushing of the skin were noted by the subjects. Neither did intravenous injections of nicotinic acid produce adverse reactions. After trying it on eleven pellagrins, whose symptoms cleared up within 24 to 72 hours, Spies reported to the Central Society for Clinical Research on November 5, 1937 that patients receiving nicotinic acid showed marked improvement without any harmful effects. Nicotinic acid proved to be an inexpensive and safe cure for pellagra. Patients did not have to remain in the hospital. They could receive nicotinic acid in tablet form to take by mouth and return to the nutrition clinic for periodic checkups. With the introduction of nicotinic acid, the death rate from pellagra declined dramatically. Three years after nicotinic acid was introduced, the death rate in 1940 was 2,040 deaths in the United States. In 1945 that figure dropped to 865. Yet not every patient had a complete remission from this therapy. And his greatest impact in working with pellagra lay in the recognition that, although nicotinic acid could cure symptoms of pellagra, multi-vitamins were necessary when patients exhibited several other nutritional deficiencies at the same time. Spies' work helped to convince the medical profession and general public the importance of nutrition and the role of vitamins in the cure of deficiency diseases. One of Spies' lasting contributions to the eradication of deficiency diseases was his involvement in fostering and promoting state and federal laws in the 1940’s, laws that required manufacturers to enrich cereal and dairy products with synthetic vitamins, thereby helping to provide a partial shield against pellagra and other nutritional deficiencies. Certainly other factors led to the defeat of pellagra: the rapid urbanization of the South after World War II, better living standards, advances in technology, new methods of preserving foods, and higher wages. But a significant contribution in the late 1930's in Birmingham, Alabama by Tom Douglas Spies with diet, vitamins, and nicotinic acid, helped finally pave the way for the conquest of "hidden hunger" in the American South.